Sermorelin
Also known as: GHRH (1-29), GRF (1-29), Geref, Sermorelin acetate
Evidence: Clinical
Overview
Synthetic GHRH(1-29) analog (Geref; FDA-approved 1997 for pediatric GH deficiency, withdrawn 2008 for commercial reasons) that restored GH and IGF-1 to young-adult levels in older men (n=10).
Sermorelin is the 29-residue N-terminal fragment of human GHRH, the shortest fragment with full GHRH activity. It was approved by the FDA in 1997 (Geref, EMD Serono) for idiopathic GH deficiency in children at 30 mcg/kg nightly, and as a 1 mcg/kg IV diagnostic; the sponsor withdrew it in 2008 for commercial reasons, not safety. In healthy older men, 1 mg twice daily for 14 days restored 24 h GH and IGF-1 to young-adult levels (Corpas 1992, n=10). Single 2 mg nightly injections for 6 weeks raised nocturnal GH and two of six strength measures but did not change IGF-1 or body composition (Vittone 1997, n=11). A 16-week trial of a related analog at 10 mcg/kg nightly raised IGF-1 28% and activated B and T cells (Khorram 1997, n=19). No approved adult indication exists; adult use is compounded and off-label.
Benefits
GH and IGF-1 restoration in older men (human, n=10), nocturnal GH and some strength measures (human, n=11), immune-cell activation (human, n=19), height velocity in GH-deficient children (human, label indication)
Dosing reference
- Research dose
- 0.5-2 mg SC per injection in adult trials (0.5-1 mg 2x daily, Corpas 1992; 2 mg nightly, Vittone 1997); pediatric label 30 mcg/kg nightly; research-community range 100-300 mcg nightly
- Range
- 500 to 2000 mcg, 1-2x daily
- Reconstitution
- 2 mL bacteriostatic water
- Common vial sizes
- 2 mg, 5 mg
Subcutaneous, given at bedtime in most adult trials; study durations ran 14 days to 16 weeks. Diagnostic use is a single 1 mcg/kg IV dose. Research protocols pair it with a GHRP; GHRH plus GHRP synergy is documented in men for GHRP-6 (Bowers 1990). Transient facial flushing and injection-site pain were the most common adverse events in trials (Prakash 1999). Intranasal bioavailability is 3-5%.
Mechanism
Sermorelin binds the GHRH receptor on anterior-pituitary somatotrophs, a Gs-coupled receptor that raises cAMP and triggers GH synthesis and release. It preserves the pulsatile pattern of GH secretion and the IGF-1 negative feedback loop (Corpas 1992). Plasma dipeptidyl peptidase IV cleaves the N-terminal Tyr-Ala, which is why the circulating half-life is a few minutes (Soule 1994). GHRPs act through the separate ghrelin receptor (GHS-R1a) and the two classes synergize (Bowers 1990).
Evidence
Clinical: at least one published human trial or an approved drug
- Restored 24 h GH and IGF-1 in healthy old men to young-adult levels at 1 mg SC twice daily for 14 days (Corpas et al., 1992)
- Single 2 mg nightly injections for 6 weeks raised nocturnal GH and some strength measures, no change in IGF-1 or body composition (Vittone et al., 1997)
- [Nle27]GHRH(1-29) 10 mcg/kg nightly for 16 weeks raised IGF-1 28% and activated B and T lymphocytes in older adults (Khorram et al., 1997)
- Increased height velocity in GH-deficient children at 30 mcg/kg nightly; 1 mcg/kg IV is a specific GH-deficiency test (Prakash and Goa, 1999)
- Human-trial status: FDA-approved 1997 (Geref) for pediatric GH deficiency and diagnosis, withdrawn 2008 for commercial reasons; no approved adult indication
References
- Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR, Journal of Clinical Endocrinology & Metabolism, 1992
- Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Vittone J, Blackman MR, Busby-Whitehead J, et al., Metabolism, 1997
- Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. Khorram O, Yeung M, Vu L, Yen SS, Journal of Clinical Endocrinology & Metabolism, 1997
- Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. Prakash A, Goa KL, BioDrugs, 1999
- Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. Soule S, King JA, Millar RP, Journal of Clinical Endocrinology & Metabolism, 1994
- Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration. Wilton P, Widlund L, Guilbaud O, Acta Paediatrica Supplement, 1993
- Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?. Walker RF, Clinical Interventions in Aging, 2006
- Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO, Journal of Clinical Endocrinology & Metabolism, 1990
Side effects
Transient facial flushing and injection-site pain were the most common adverse events in pediatric and adult trials (Prakash 1999); no significant adverse effects in 6 weeks of 2 mg nightly dosing (Vittone 1997). Headache, dizziness, water retention, joint aches and reduced insulin sensitivity are commonly reported (anecdotal) with sustained GH elevation.
Storage
- Storage
- Refrigerated (2-8°C)
- Lyophilized
- 24+ months at room temperature
- Reconstituted
- 28-30 days refrigerated
Pharmacology
- Half-life
- ~4 min disappearance half-time (human, IV infusion; Soule 1994); GH stays elevated ~3 h after an IV dose (Wilton 1993)
- Bioavailability
- Intranasal 3-5% (human; Wilton 1993); SC absolute bioavailability not reported in located literature
- Molecular weight
- 3357.88 Da
- Sequence
- YADAIFTNSYRKVLGQLSARKLLQDIMSR[NH2]